Improved Bioavailability with Dry Powder Cannabidiol Inhalation: A Phase 1 Clinical Study.

Oral cannabidiol (CBD) is approved by the Food and Drug Administration (FDA) to treat patients with Dravet and Lennox-Gastaut syndromes and tuberous sclerosis complex. The therapeutic potential of oral CBD formulations is limited by extensive first-pass hepatic metabolism. Following oral administration, the inactive metabolite blood concentration is ∼40-fold higher than CBD. Inhalation bypasses the pharmacokinetic (PK) variability attributed to irregular gastrointestinal absorption and first-pass hepatic metabolism and may efficiently deliver CBD into systemic circulation. This phase 1 study compared the PK of a dry-powder inhaler (DPI) CBD formulation (10 mg powder containing 2.1 mg CBD) with an oral CBD solution (Epidiolex®, 50 mg) in healthy participants. Following a single dose of Epidiolex or DPI CBD (n=10 PK evaluable participants each), the maximum CBD concentration for the inhaled powder was 71-fold higher than that of Epidiolex while administering 24-fold less CBD. The mean time to reach maximum concentration was 3.8 min for the DPI CBD formulation compared with 122 min for Epidiolex. Both Epidiolex and DPI CBD were generally safe and well-tolerated. These data indicate that DPI CBD provided more rapid onset and increased bioavailability than oral CBD and support further investigations on the use of DPI CBD for acute indications.

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Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of Competing Interest O. Devinsky receives grant support from NINDS, NIMH, MURI, CDC and NSF. He has equity and/or compensation from the following companies: Receptor Holdings Inc, Tilray, Qstate Biosciences, Tevard Biosciences, Empatica, Engage (acquired by UCB, Inc.), Papa & Barkley, Rettco, SilverSpike, and California Cannabis Enterprises and has received consulting fees from GW Pharma, Cavion (acquired by Jazz Pharmaceuticals), and Zogenix. K. Kraft and A. Leone-Bay are employees of Receptor Life Sciences. L. Rusch is an employee of Cardiovascular Clinical Sciences. M. Fein is an employee of High Point Clinical Trials Center.